| First Author | Hess A | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 9 | Pages | 3731-6 |
| PubMed ID | 21245297 | Mgi Jnum | J:170620 |
| Mgi Id | MGI:4946985 | Doi | 10.1073/pnas.1011774108 |
| Citation | Hess A, et al. (2011) Blockade of TNF-alpha rapidly inhibits pain responses in the central nervous system. Proc Natl Acad Sci U S A 108(9):3731-6 |
| abstractText | There has been a consistent gap in understanding how TNF-alpha neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-alpha acts through the CNS before directly affecting joint inflammation. Through use of functional MRI (fMRI), we demonstrate that within 24 h after neutralization of TNF-alpha, nociceptive CNS activity in the thalamus and somatosensoric cortex, but also the activation of the limbic system, is blocked. Brain areas showing blood-oxygen level-dependent signals, a validated method to assess neuronal activity elicited by pain, were significantly reduced as early as 24 h after an infusion of a monoclonal antibody to TNF-alpha. In contrast, clinical and laboratory markers of inflammation, such as joint swelling and acute phase reactants, were not affected by anti-TNF-alpha at these early time points. Moreover, arthritic mice overexpressing human TNF-alpha showed an altered pain behavior and a more intensive, widespread, and prolonged brain activity upon nociceptive stimuli compared with wild-type mice. Similar to humans, these changes, as well as the rewiring of CNS activity resulting in tight clustering in the thalamus, were rapidly reversed after neutralization of TNF-alpha. These results suggest that neutralization of TNF-alpha affects nociceptive brain activity in the context of arthritis, long before it achieves anti-inflammatory effects in the joints. |
